Displaying publications 41 - 50 of 50 in total

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  1. Tan HL, Zain SM, Eng HS, Mohamed Z, Mahadeva S, Chan WK, et al.
    PMID: 32410320 DOI: 10.1111/hepr.13525
    AIM: Human leukocyte antigen (HLA) regions were highlighted as important genetic markers for various liver diseases by hepatology-related genome-wide association studies. Replication studies in non-alcoholic fatty liver disease (NAFLD) are limited and none has investigated the association of HLA alleles with non-alcoholic steatohepatitis (NASH) and other histological characteristics. In the current study, we examined the association of HLA-DQA1 and HLA-DQB1 alleles with NAFLD spectrum and its histological characteristics.

    METHODS: Consecutive biopsy-proven NAFLD patients (n = 191) and healthy controls (n = 188) were enrolled and genotyped for HLA-DQA1 and HLA-DQB1 alleles using the sequence-specific oligonucleotide-polymerase chain reaction method.

    RESULTS: No association was found between the HLA alleles and NAFLD or NASH in a case-control setting. Nevertheless, among NAFLD patients, the frequency of HLA-DQB1*06 allele was significantly the lowest in NASH with significant fibrosis (10.4%) and approximately similar for NASH without significant fibrosis (22.9%) and NAFL (22.5%) (P = 0.004). It is noteworthy that the association remains significant after correction for multiple comparisons (Pc  = 0.04). Multivariate analysis revealed that HLA-DQB1*06 allele is also associated with fibrosis score (P = 0.001); the result remains significant after correction for multiple comparisons.

    CONCLUSION: These findings suggest that HLA-DQB1*06 is associated with lower fibrosis score in NAFLD patients.

  2. Pushpamalar J, Meganathan P, Tan HL, Dahlan NA, Ooi LT, Neerooa BNHM, et al.
    Gels, 2021 Sep 27;7(4).
    PMID: 34698125 DOI: 10.3390/gels7040153
    Delivering a drug to the target site with minimal-to-no off-target cytotoxicity is the major determinant for the success of disease therapy. While the therapeutic efficacy and cytotoxicity of the drug play the main roles, the use of a suitable drug delivery system (DDS) is important to protect the drug along the administration route and release it at the desired target site. Polysaccharides have been extensively studied as a biomaterial for DDS development due to their high biocompatibility. More usefully, polysaccharides can be crosslinked with various molecules such as micro/nanoparticles and hydrogels to form a modified DDS. According to IUPAC, hydrogel is defined as the structure and processing of sols, gels, networks and inorganic-organic hybrids. This 3D network which often consists of a hydrophilic polymer can drastically improve the physical and chemical properties of DDS to increase the biodegradability and bioavailability of the carrier drugs. The advancement of nanotechnology also allows the construction of hydrogel DDS with enhanced functionalities such as stimuli-responsiveness, target specificity, sustained drug release, and therapeutic efficacy. This review provides a current update on the use of hydrogel DDS derived from polysaccharide-based materials in delivering various therapeutic molecules and drugs. We also highlighted the factors that affect the efficacy of these DDS and the current challenges of developing them for clinical use.
  3. Wong JJM, Tan HL, Sultana R, Ma YJ, Aguilan A, Lee SW, et al.
    Front Pediatr, 2022;10:993175.
    PMID: 36483473 DOI: 10.3389/fped.2022.993175
    BACKGROUND: The longitudinal course of patients with pediatric acute respiratory distress syndrome (PARDS) is not well described. In this study, we describe the oxygenation index (OI) and oxygen saturation index (OSI) in mild, moderate, and severe PARDS over 28 days and provide pilot data for the time to resolution of PARDS (T res), as a short-term respiratory-specific outcome, hypothesizing that it is associated with the severity of PARDS and clinical outcomes.

    METHODS: This prospective observational study recruited consecutive patients with PARDS. OI and OSI were trended daily over 28 days. T res (defined as OI 

  4. Vardar E, Nam HY, Vythilingam G, Tan HL, Mohamad Wali HA, Engelhardt EM, et al.
    Int J Mol Sci, 2023 Nov 29;24(23).
    PMID: 38069268 DOI: 10.3390/ijms242316945
    The effective and long-term treatment of cartilage defects is an unmet need among patients worldwide. In the past, several synthetic and natural biomaterials have been designed to support functional articular cartilage formation. However, they have mostly failed to enhance the terminal stage of chondrogenic differentiation, leading to scar tissue formation after the operation. Growth factors substantially regulate cartilage regeneration by acting on receptors to trigger intracellular signaling and cell recruitment for tissue regeneration. In this study, we investigated the effect of recombinant insulin-like growth factor 1 (rIGF-1), loaded in fibrin microbeads (FibIGF1), on cartilage regeneration. rIGF-1-loaded fibrin microbeads were injected into full-thickness cartilage defects in the knees of goats. The stability, integration, and quality of tissue repair were evaluated at 1 and 6 months by gross morphology, histology, and collagen type II staining. The in vivo results showed that compared to plain fibrin samples, particularly at 6 months, FibIGF1 improved the functional cartilage formation, confirmed through gross morphology, histology, and collagen type II immunostaining. FibIGF1 could be a promising candidate for cartilage repair in the clinic.
  5. Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al.
    BMC Infect Dis, 2018 05 21;18(1):232.
    PMID: 29783955 DOI: 10.1186/s12879-018-3141-6
    BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors.

    METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue.

    RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender).

    CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

  6. A Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Aizat WM, Ho KL, Teh AH, et al.
    PeerJ, 2018;6:e5377.
    PMID: 30280012 DOI: 10.7717/peerj.5377
    Proteins of the DUF866 superfamily are exclusively found in eukaryotic cells. A member of the DUF866 superfamily, C1ORF123, is a human protein found in the open reading frame 123 of chromosome 1. The physiological role of C1ORF123 is yet to be determined. The only available protein structure of the DUF866 family shares just 26% sequence similarity and does not contain a zinc binding motif. Here, we present the crystal structure of the recombinant human C1ORF123 protein (rC1ORF123). The structure has a 2-fold internal symmetry dividing the monomeric protein into two mirrored halves that comprise of distinct electrostatic potential. The N-terminal half of rC1ORF123 includes a zinc-binding domain interacting with a zinc ion near to a potential ligand binding cavity. Functional studies of human C1ORF123 and its homologue in the fission yeast Schizosaccharomyces pombe (SpEss1) point to a role of DUF866 protein in mitochondrial oxidative phosphorylation.
  7. Maran S, Ee R, Faten SA, Sy Bing C, Khaw KY, Erin Lim SH, et al.
    PLoS One, 2020;15(4):e0230982.
    PMID: 32315303 DOI: 10.1371/journal.pone.0230982
    Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
  8. Bakar KA, Muhamad NA, Sarpin MA, Shaharudin S, Sidhu S, Yap SL, et al.
    Pediatr Nephrol, 2023 Jun;38(6):1897-1905.
    PMID: 36272027 DOI: 10.1007/s00467-022-05774-0
    BACKGROUND: The PedsQL 3.0 End Stage Renal Disease (ESRD) Module is a well-accepted instrument internationally but it is not available in the local language. We aimed to validate the Bahasa Melayu (Malay language) version and determine the health-related quality of life (HRQoL) scores amongst children with CKD in Malaysia.

    METHODS: The source questionnaire in English was translated into Bahasa Melayu. Linguistic validation guidelines by the MAPI Research Institute were followed. The already validated Bahasa Melayu PedsQL 4.0 Generic Core Scales was used for comparison. Sociodemographic data were collected during the interview. Statistical analyses were performed using SPSS version 25.0.

    RESULTS: Sixty-nine children aged 8 to 18 with CKD stages 4 and 5, with or without dialysis, and their caregivers were recruited. Mean age was 12.62 ± 2.77 (SD). Evaluation of the PedsQL 3.0 ESRD Module Bahasa Melayu version demonstrated good internal consistency (Cronbach alpha 0.82). There was good agreement between child self-report and parent proxy report in all domains; average intraclass correlation coefficients (ICC) were 0.78, 95% CI (0.71, 0.84). Scores obtained from Generic 4.0 scales correlated with the disease-specific ESRD 3.0 scale, Spearman's rho = 0.32, p = 0.007. The Kruskal-Wallis H test indicated that there were no significant differences between stages of CKD and their respective mean HRQoL score, χ2(2) = 2.88, p = 0.236.

    CONCLUSIONS: The PedsQL 3.0 ESRD Module Bahasa Melayu version is a reliable and feasible tool for cross-cultural adaptation. A longer prospective study may help better illustrate the quality of life in this group of children.

  9. Mohd Yunus SS, Nabil S, Rashdi MF, Nazimi AJ, Nordin R, Tan HL, et al.
    Antibiotics (Basel), 2023 Apr 02;12(4).
    PMID: 37107058 DOI: 10.3390/antibiotics12040696
    This study explores the opinions of Malaysian clinical specialists on the antibiotic prophylaxis against infective endocarditis (IE) as described in the 2008 National Institute for Health and Care Excellence (NICE) guideline. This cross-sectional study was performed from September 2017 to March 2019. The self-administered questionnaire comprised two sections: background information of the specialists and their opinions on the NICE guideline. The questionnaire was distributed to 794 potential participants, and 277 responded (response rate of 34.9%). In general, 49.8% of the respondents believed that clinicians should adhere to the guideline, although the majority of oral and maxillofacial surgeons (54.5%) actually disagreed with this view. The dental procedures that were perceived as presented moderate-to-high risk for IE were minor surgery for an impacted tooth with a recent episode of infection, dental implant surgery, periodontal surgery and dental extraction in patients with poor oral hygiene. The cardiac conditions that were strongly recommended for antibiotic prophylaxis were severe mitral valve stenosis or regurgitation and previous IE. Less than half of Malaysian clinical specialists agreed with the changes in the 2008 NICE guideline, contributing to their insistence that antibiotic prophylaxis is still needed for high-risk cardiac conditions and selected invasive dental procedures.
  10. Phua J, Lim CM, Faruq MO, Nafees KMK, Du B, Gomersall CD, et al.
    J Intensive Care, 2021 Oct 07;9(1):60.
    PMID: 34620252 DOI: 10.1186/s40560-021-00574-4
    BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia.

    MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty.

    CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

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